Targeted delivery of curcumin based on nanocarriers: potential therapeutic strategies for noninfectious arthritis.

The evidence base that underlies the management of children and young people with paediatric rheumatic diseases is deficient. In this field, there are many crucial unanswered questions. The UK Paediatric Rheumatology Clinical Studies Group, supported by UK National Institute for Health Research Clinical Research Network: children and Versus Arthritis, elicited ideas for research priorities from paediatric rheumatologists, trainees, allied health-care professionals, nurse specialists, patients, parents of patients, carers, and charities. These ideas were collected through online surveys and face-to-face meetings. A modified Delphi process was used, which included online research priority ranking surveys and a consensus workshop. A longlist of 55 disease-specific research priorities and 37 general research priorities were voted on in the first survey. A list of 11 top general research priorities was produced. The top ten disease-specific research priorities were discussed in depth at a Delphi workshop to determine their final ranking. This Health Policy paper will help to guide clinicians, academics, and funding bodies to prioritise research in paediatric rheumatic diseases, specifically in areas of unmet patient needs.

1. Jane G. Schaller, MD* 1. 2. *David and Leona Karp Professor of Pediatrics; Chair, Department of Pediatrics, Tufts University School of Medicine, Boston, MA. 1. There are several recognizable subgroups of juvenile rheumatoid arthritis (JRA): systemic-onset, polyarticular, pauciarticular, and late childhood onset. 2. Rheumatoid factor usually is negative in JRA. 3. Systemic-onset JRA is characterized by high intermittent fevers and other extra-articular manifestations: lymphadenopathy, rash, pleuritis, and pericarditis. 4. Iridocyclitis is absent in acute-onset disease but common in patients who have pauciarticular disease. 5. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the front-line and important agents in the therapy of patients who have JRA. 6. Controlled studies show that d-penicillamine, hydroxychloroquine, and oral gold are no more effective than placebo in the treatment of JRA. Juvenile rheumatoid arthritis (JRA) is a term used to describe the condition of chronic synovitis in children of which there are several distinct subgroups. Chronic synovitis in children was first described well in the English literature in 1897 by George Frederick Still, an English pediatrician and pathologist, who reported on 23 children who had chronic arthritis and came to his attention while he was training at the Hospital for Sick Children, Great Ormond Street. Still postulated that several separate conditions were responsible for chronic arthritis in children. Little subsequent work in this area was pursued until the late 1940s. Most modern observers have come to agree with Still that chronic arthritis in children encompasses several distinct disease subgroups (Table 1⇓ ). The relationship of JRA to adult rheumatoid arthritis was uncertain for many years. Now it seems clear that the classic adult-type rheumatoid arthritis does occur in children but is quite rare, the JRA subgroups seronegative 1 polyarthritis and systemic-onset disease also occur in adults but not frequently, the pauciarthritis of early childhood has not been recognized in adults, and the pauciarthritis of older children usually is classified as spondyloarthropathy in adults. The nomenclature for chronic childhood arthritis remains confusing (Table 2⇓), but …

The role of type I and type III interferons (IFNs) in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) is still poorly understood. The objective of this study was to examine the hypothesis that IFN expression profiles in the peripheral blood differ between subsets of arthritic subjects. Multiple type I and type III IFNs were examined in patients with RA and JIA, as well as among subtypes of JIA. Treatment-naïve RA and JIA patients were enrolled. Droplet digital PCR was used to measure the expression of type I, II, and III interferons in blood and synovial fluid leukocytes. Dendritic cell subsets were isolated from synovial fluid to examine IFN expression in each subset. Additionally, synovial mononuclear cells and JIA-derived fibroblast-like synoviocytes were stimulated with TNF, IFNγ, and poly(I:C) to examine inducible IFN expression. The predominant type I IFN gene expressed by blood leukocytes was IFNκ and was significantly lower in RA than JIA and controls. Oligoarticular and psoriatic JIA subgroups showed higher IFNκ expression compared to polyarticular JIA and RA. JIA synovial fluid leukocytes expressed abundant IFNγ and type III IFNs (IFNλ1, IFNλ3), with distinct dendritic cell subset contributions. JIA fibroblast-like synoviocytes produced IFNβ, IFNλ1, and IFNλ2 mRNA upon poly(I:C) stimulation. This study revealed differences in IFN expression patterns in RA and JIA, with notable differences between JIA subtypes. The expression levels of IFNκ, IFNγ, IFNλ1 and IFNλ3 in JIA suggest specific roles in disease pathology, influenced by disease subtype and joint microenvironment. This study contributes to understanding IFN-mediated mechanisms in arthritis, potentially guiding targeted therapeutic strategies.

Paired samples of serum and synovial fluid (SF) from 13 patients with juvenile rheumatoid arthritis (JRA) and 10 patients with adult rheumatoid arthritis (RA) were examined regarding the level of immunoglobulins and the occurrence and titres of anti-IgG antibodies and antinuclear antibodies (ANA). The levels of immunoglobulins were lower in SF than in serum. In JRA the SF/serum ratio of IgG was equal to that of albumin, pointing to a local production of IgG. The SF/serum ratio of IgM was equal to that of alpha 2-macroglobulin. In JRA the SF/serum ratios of immunoglobulins tended to be lower than in RA, the difference being significant for IgM. IgD autoantibodies and IgA anti-IgG were not found in JRA. IgE autoantibodies occurred in some cases, but in RA in more than 60%. In JRA the SF titres of anti-IgG and ANA were most often lower than the serum titres. In RA the SF titres were often higher than the serum titres. In 9 of 10 paired SF samples from patients with RA the SF/serum ratios were mutually different with regard to one or several immunoglobulins. Evidence of synovial production of anti-IgG antibodies of classes other than IgG distinguished RA from JRA. Otherwise the differences were quantitative.

To compare the effectiveness of tumor necrosis factor inhibitors (TNFi) ± comedication and methotrexate (MTX) monotherapy between patients with adult juvenile idiopathic arthritis (JIA) and patients with rheumatoid arthritis (RA). Adult patients with JIA and RA were identified from the Norwegian Antirheumatic Drug Register (NOR-DMARD) register. Disease activity measurements at baseline, 3, 6, and 12 months were compared between patients with JIA and RA starting (1) TNFi and (2) MTX monotherapy, using age- and gender-weighted analyses. We calculated differences between JIA and RA in mean changes in Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI), among other disease activity measures. DAS28, CDAI, SDAI, and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission rates at 3, 6, and 12 months, as well as 6- and 12-month Lund Efficacy Index (LUNDEX)-corrected rates, were calculated. We identified 478 patients with JIA (TNFi/MTX monotherapy, n = 358/120) and 4637 patients with RA (TNFi/MTX monotherapy, n = 2292/2345). Patients with JIA had lower baseline disease activity compared to patients with RA across treatment groups. After baseline disease activity adjustment, there were no significant differences in disease activity change from baseline to 3, 6, and 12-months of follow-up between patients with JIA and RA for either treatment group. Twelve-month remission rates were similar between groups based on DAS28 (TNFi: JIA 55.2%, RA 49.5%; MTX monotherapy: JIA 45.3%, RA 41.2%) and ACR/EULAR remission criteria (TNFi: JIA 20.4%, RA 20%; MTX monotherapy: JIA 17%, RA 12.7%). Median drug survival (yrs) was similar for JIA and RA in both treatment groups (TNFi: JIA 1.2, RA 1.4; MTX monotherapy: JIA 1.3, RA 1.6). TNFi and MTX monotherapy are effective in adult JIA, with similar effectiveness to that shown in RA.

Fungal Infections Complicating Tumor Necrosis Factor α Blockade Therapy

Objective To compare the positive rate of anti-mutant citrulline vimentin (MCV) antibody and anti-cyclic citrullinated peptide (CCP) antibody in serum of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). To investigate the diagnostic value and significance of anti-MCV and anti-CCP antibody in these two diseases. Methods Anti-CCP and anti-MCV antibodies were detected by enzyme-linked immunosorbent assay(ELISA). The serum samples were from 113 patients with JIA, 632 patients with RA, 102 adult without RA and 56 children without RA. Chi-square test and multiple comparisons were used for statistical analysis. Results ① In RA patients, the sensitivity, specificity and area under the receiver operating characteristic curve (ROC curve) of anti-MCV antibody was 90.2%, 91.2%, 0.919; the sensitivity, specificity and area under the ROC curve of anti-CCP antibody was 92.6%, 93.1% and 0.934. In JIA, the specificity of antibodies was 98.2%, the sensitivity was low. Area under the ROC curve of anti-MCV antibody was 0.579. Area under the ROC curve of anti-CCP antibody was 0.561. ② The positive rate of anti-MCV antibody in RA was 90.2%, which was higher than that of JIA (16.8%) (P<0.01). The positive rate of anti-CCP antibody in RA was 92.2%, which was higher than that of JIA (14.2%) (P<0.01). The positive rates of anti-MCV antibody in JIA with RF-negative polyarthrosis, RF-positive polyarthrosis, systemic type, oligo-joint type, attachment points, unclassified was 11.8%, 69.2%, 14.3%, 17.4%, 3.6%, 0. The positive rate of anti-CCP was 11.8%, 61.5%, 14.3%, 13.0%, 0 and 0 prespectively. For anti-MCV antibody, the chi-square values in patients with RA between RF-negative polyarthrosis, RF-positive olyarthrosis, systemic type, oligo-joint type, attachment points, unclassified arthritis were 160.2, 4.02, 34.4, 102.0, 165.1 and 57.0 respectively. There were significant differences between RA and all types of JIA (P<0.05). The positive rate of anti-CCP antibody in patients with RA between RF-negative polyarthrosis, RF-positive polyarthrosis, systemic type, iligo-joint type, attachment points, unclassified arthritis were 192.3, 11.9, 44.0, 139.4, 212.5 and 71.9. There were significant differences between RA and all types of JIA (P<0.05). Conclusion The diagnostic value of anti-MCV and anti-CCP antibodies is high in RA. Anti-MCV and anti-CCP antibody have certain diagnostic value of JIA. The positive rates of anti-MCV and anti-CCP antibody in the types in JIA are lower than those of RA patients. Key words: Arthritis, rheumatoid; Arthritis, juvenile rheumatoid; Antibodies

Invited Commentary

Predictive significance of CXCL8, CXCL10 and CXCL16 in juvenile idiopathic and rheumatoid arthritis Iraqi patients

Introduction: Evolution of inflammatory arthritis from innate to adaptive immune mechanisms.

Background/Aims Patients with inflammatory rheumatic diseases (IRD) have an increased risk of adverse pregnancy outcomes (APO), although the comparative risk of APO in rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) pregnancies has not been directly compared. Therefore, this study examined pregnancy outcomes (PO) of subjects with RA, JIA, and SLE, who had all received pre-pregnancy counselling to ensure disease control, to identify whether there are any differences in APO between each individual IRD group. Pregnancy outcomes were compared with healthy pregnant subjects lacking IRD, to determine the comparative risk of APO in RA, JIA and SLE pregnancies. Methods A prospective case-controlled study was conducted at University College London Hospital from February 2018 to February 2021. A total of 183 patients were enrolled into the study, consisting of 120 pregnant patients including 60 patients with an IRD (n = 29 RA, n = 12 JIA and n = 19 SLE), 60 pregnant patients without any IRD and 63 non-pregnant patients with IRD (n = 30 RA, n = 12 JIA, n = 21 SLE). Pregnancy outcome data was obtained from all pregnant patients and the individual IRD groups’ outcomes were compared to each other and against outcomes from pregnancies without an IRD. Results Patients were predominantly Caucasian, ranging from 17-45 years of age. Of 111 reported PO, 99.09% (n = 110) resulted in a live birth (n = 27 (100.00%) RA, n = 11 (100.00%) JIA, n = 18 (94.74%) SLE versus n = 54 (100.00%) pregnancies without IRD). Overall, 5.56% (n = 1 SLE pregnancy) resulted in a spontaneous early trimester miscarriage, 6.36% (n = 7) were pre-term births (n = 3 (11.11%) RA, n = 1 (9.09%) JIA, n = 2 (11.11) SLE pregnancies versus n = 1 (1.85%) pregnancy without IRD). No stillbirths/foetal deaths were reported. Only two maternal complications were reported (n = 1 Group B strep infection, n = 1 gestational diabetes in RA pregnancies). In total six foetal complications were observed in four RA (n = 1 each for enlarged kidney, tongue tied, neonatal jaundice and Group B strep infection), n = 1 JIA (tongue tied) and n = 1 SLE (prolapsed cord) pregnancies. In relation to disease activity statuses in pregnancy, the majority of IRD pregnant patients were in remission (n = 42 (73.68%), n = 18 RA, n = 6 JIA and n = 18 SLE), 28 (49.12%) IRD patients had low disease activity (n = 8 RA, n = 2 JIA and n = 18 SLE) and nine (15.79%) had moderate/high disease activity (n = 6 RA, n = 2 JIA and n = 1 SLE). Only two (3.51%) RA patients reported disease flares during pregnancy, whereas no JIA/SLE patients experienced any flares. Conclusion This first prospective case-controlled study of RA, JIA, SLE and healthy pregnancies has identified favourable and comparable PO between IRD pregnancies with good disease control. This study highlights the importance and need for IRD pregnant women to undergo pre-pregnancy counselling and maintenance of disease control during pregnancy to enhance the chances of successful pregnancy outcomes. Disclosure H. Nguyen: None. D.A. Isenberg: Consultancies; AstraZeneca, Merck Serono, Eli Lilly, Servier, Genentech. D.J. Williams: Grants/research support; National Institute for Health Research University College London Hospitals Biomedical Research Centre. I. Giles: Grants/research support; UCB Pharma.

&lt;p dir="ltr"&gt;Chronic inflammatory diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) can have lasting effects on individuals' ability to work and earn a living. While advancements in treatment have improved disease management, their impact on long-term economic outcomes remains uncertain. This thesis examines how RA and JIA affect earnings, work loss, and educational attainment, using Swedish nationwide register data. Individuals with RA and JIA were matched to same-sex siblings (RA) or general population comparators (JIA) based on birth year, sex, and location.&lt;/p&gt;&lt;p dir="ltr"&gt;Study I compared the earnings of 2,433 RA patients (2006–2017) to those of their same-sex siblings. We found that patients with RA, compared to siblings, earned 5.4% less per year after diagnosis. Stratifying by diagnosis year demonstrated a more pronounced reduction among those diagnosed earlier (2006–2010) (8.2%). Patients diagnosed more recently (2011–2017) showed no statistically significant earnings decline, suggesting that improved treatment and earlier intervention may have mitigated economic losses.&lt;/p&gt;&lt;p dir="ltr"&gt;Study II investigated work loss, measured as sick leave and disability pension, in a similar RA cohort diagnosed between 2006 and 2020, with slightly extended inclusion and follow-up compared to Study I. In the first year after diagnosis, patients diagnosed between 2006 and 2011 had 47 additional days of work loss per year, and patients diagnosed between 2012 and 2020 had 26 additional days of work loss per year. Work loss was highest in both cohorts in the first year after diagnosis but declined over time. From years 2 to 10 after diagnosis, patients diagnosed between 2006 and 2011 had an additional 29 days annually, and patients diagnosed between 2012 and 2020 had an additional 11 days annually.&lt;/p&gt;&lt;p dir="ltr"&gt;Study III focused on earnings and work loss in 4,737 individuals diagnosed with JIA, matched to 23,645 general population comparators (2001–2017). Patients with JIA had 5.5% lower earnings than their peers, with the largest gap occurring before age 26. While earnings differences diminished over time, work loss remained consistently higher, with patients with JIA having an average of 11 additional sick leave or disability days per year. A subgroup with more severe disease accounted for the majority of work loss. Among those with systemic JIA (sJIA), a particularly severe form of the disease, work loss was even higher, and earnings were lower compared to other patients with JIA.&lt;/p&gt;&lt;p dir="ltr"&gt;Study IV examined educational attainment among 4,254 individuals diagnosed with JIA (2001–2017), matched to 4,254 general population comparators. Over up to 16 years of follow-up (median 4 years), 83.1% of patients with JIA and 83.0% of comparators completed high school or more (hazard ratio [HR] 0.99, 95% CI: 0.97–1.01). Similarly, 34.5% of patients and 34.1% of comparators pursued some post-secondary education or more (HR 1.02, 95% CI: 0.97–1.08). No differences were observed by sex, parental education, or diagnosis period. Among individuals followed until age 30, educational outcomes remained comparable: 85.9% of patients with JIA and 86.1% of comparators completed high school, and 48.1% versus 49.9% had post-secondary education. The conditional odds ratio was 0.98 (95% CI: 0.71–1.36) for a high school degree and 0.92 (95% CI: 0.73–1.15) for post-secondary education.&lt;/p&gt;&lt;p dir="ltr"&gt;To summarize, we found clear improvements in earnings and work loss among patients with RA diagnosed in more recent years, though work loss remained elevated overall, driven by a small subset of patients. In JIA, earnings and employment were lower than those of the general population comparators, with the differences narrowing after age 26. Patients with JIA had consistently higher work loss, about 11 additional days per year, also driven by a more severely affected subgroup. Educational attainment in patients with JIA was comparable to the general population, with similar proportions completing high school or post-secondary education by age 30. These findings suggest that advances in diagnosis and treatment may have improved long-term socioeconomic outcomes.&lt;/p&gt;&lt;h3&gt;List of scientific papers&lt;/h3&gt;&lt;p dir="ltr"&gt;I. &lt;b&gt;Miller H&lt;/b&gt;, Neovius M, Askling J, Bruze G. Impact of Incident Rheumatoid Arthritis on Earnings: A Nationwide Sibling Comparison Study. Rheumatology (Oxford). 2024 Oct 16:keae535. Epub ahead of print. Erratum in: Rheumatology (Oxford). 2025 Jan 06. &lt;a href="https://doi.org/10.1093/rheumatology/keae535" rel="noreferrer" target="_blank"&gt;https://doi.org/10.1093/rheumatology/keae535&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;II. &lt;b&gt;Miller H&lt;/b&gt;, Bruze G, Johansson K, Askling J, Neovius M. Incident Rheumatoid Arthritis and Work Loss: A Nationwide Sibling Comparison Study. [Submitted]&lt;/p&gt;&lt;p dir="ltr"&gt;III. &lt;b&gt;Miller H&lt;/b&gt;, Neovius M, Sundberg E, Askling J, Bruze G. Juvenile Idiopathic Arthritis, Earnings and Work Loss: A Nationwide Matched Cohort Study. Arthritis Care Res (Hoboken). 2025 Mar 16. doi:10.1002/acr.25522. Epub ahead of print. &lt;a href="https://doi.org/10.1002/acr.25522" rel="noreferrer" target="_blank"&gt;https://doi.org/10.1002/acr.25522&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;IV. &lt;b&gt;Miller H&lt;/b&gt;, Neovius M, Johansson K, Askling J, Bruze G. Juvenile Idiopathic Arthritis and Attained Education: A Nationwide Matched Cohort Study. [Manuscript]&lt;/p&gt;

&lt;p dir="ltr"&gt;Chronic inflammatory diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) can have lasting effects on individuals' ability to work and earn a living. While advancements in treatment have improved disease management, their impact on long-term economic outcomes remains uncertain. This thesis examines how RA and JIA affect earnings, work loss, and educational attainment, using Swedish nationwide register data. Individuals with RA and JIA were matched to same-sex siblings (RA) or general population comparators (JIA) based on birth year, sex, and location.&lt;/p&gt;&lt;p dir="ltr"&gt;Study I compared the earnings of 2,433 RA patients (2006–2017) to those of their same-sex siblings. We found that patients with RA, compared to siblings, earned 5.4% less per year after diagnosis. Stratifying by diagnosis year demonstrated a more pronounced reduction among those diagnosed earlier (2006–2010) (8.2%). Patients diagnosed more recently (2011–2017) showed no statistically significant earnings decline, suggesting that improved treatment and earlier intervention may have mitigated economic losses.&lt;/p&gt;&lt;p dir="ltr"&gt;Study II investigated work loss, measured as sick leave and disability pension, in a similar RA cohort diagnosed between 2006 and 2020, with slightly extended inclusion and follow-up compared to Study I. In the first year after diagnosis, patients diagnosed between 2006 and 2011 had 47 additional days of work loss per year, and patients diagnosed between 2012 and 2020 had 26 additional days of work loss per year. Work loss was highest in both cohorts in the first year after diagnosis but declined over time. From years 2 to 10 after diagnosis, patients diagnosed between 2006 and 2011 had an additional 29 days annually, and patients diagnosed between 2012 and 2020 had an additional 11 days annually.&lt;/p&gt;&lt;p dir="ltr"&gt;Study III focused on earnings and work loss in 4,737 individuals diagnosed with JIA, matched to 23,645 general population comparators (2001–2017). Patients with JIA had 5.5% lower earnings than their peers, with the largest gap occurring before age 26. While earnings differences diminished over time, work loss remained consistently higher, with patients with JIA having an average of 11 additional sick leave or disability days per year. A subgroup with more severe disease accounted for the majority of work loss. Among those with systemic JIA (sJIA), a particularly severe form of the disease, work loss was even higher, and earnings were lower compared to other patients with JIA.&lt;/p&gt;&lt;p dir="ltr"&gt;Study IV examined educational attainment among 4,254 individuals diagnosed with JIA (2001–2017), matched to 4,254 general population comparators. Over up to 16 years of follow-up (median 4 years), 83.1% of patients with JIA and 83.0% of comparators completed high school or more (hazard ratio [HR] 0.99, 95% CI: 0.97–1.01). Similarly, 34.5% of patients and 34.1% of comparators pursued some post-secondary education or more (HR 1.02, 95% CI: 0.97–1.08). No differences were observed by sex, parental education, or diagnosis period. Among individuals followed until age 30, educational outcomes remained comparable: 85.9% of patients with JIA and 86.1% of comparators completed high school, and 48.1% versus 49.9% had post-secondary education. The conditional odds ratio was 0.98 (95% CI: 0.71–1.36) for a high school degree and 0.92 (95% CI: 0.73–1.15) for post-secondary education.&lt;/p&gt;&lt;p dir="ltr"&gt;To summarize, we found clear improvements in earnings and work loss among patients with RA diagnosed in more recent years, though work loss remained elevated overall, driven by a small subset of patients. In JIA, earnings and employment were lower than those of the general population comparators, with the differences narrowing after age 26. Patients with JIA had consistently higher work loss, about 11 additional days per year, also driven by a more severely affected subgroup. Educational attainment in patients with JIA was comparable to the general population, with similar proportions completing high school or post-secondary education by age 30. These findings suggest that advances in diagnosis and treatment may have improved long-term socioeconomic outcomes.&lt;/p&gt;&lt;h3&gt;List of scientific papers&lt;/h3&gt;&lt;p dir="ltr"&gt;I. &lt;b&gt;Miller H&lt;/b&gt;, Neovius M, Askling J, Bruze G. Impact of Incident Rheumatoid Arthritis on Earnings: A Nationwide Sibling Comparison Study. Rheumatology (Oxford). 2024 Oct 16:keae535. Epub ahead of print. Erratum in: Rheumatology (Oxford). 2025 Jan 06. &lt;a href="https://doi.org/10.1093/rheumatology/keae535" rel="noreferrer" target="_blank"&gt;https://doi.org/10.1093/rheumatology/keae535&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;II. &lt;b&gt;Miller H&lt;/b&gt;, Bruze G, Johansson K, Askling J, Neovius M. Incident Rheumatoid Arthritis and Work Loss: A Nationwide Sibling Comparison Study. [Submitted]&lt;/p&gt;&lt;p dir="ltr"&gt;III. &lt;b&gt;Miller H&lt;/b&gt;, Neovius M, Sundberg E, Askling J, Bruze G. Juvenile Idiopathic Arthritis, Earnings and Work Loss: A Nationwide Matched Cohort Study. Arthritis Care Res (Hoboken). 2025 Mar 16. doi:10.1002/acr.25522. Epub ahead of print. &lt;a href="https://doi.org/10.1002/acr.25522" rel="noreferrer" target="_blank"&gt;https://doi.org/10.1002/acr.25522&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;IV. &lt;b&gt;Miller H&lt;/b&gt;, Neovius M, Johansson K, Askling J, Bruze G. Juvenile Idiopathic Arthritis and Attained Education: A Nationwide Matched Cohort Study. [Manuscript]&lt;/p&gt;

Objective: The incidence and clinical significance of anti‐cyclic citrullinated peptide (CCP) antibodies in a cohort of Chinese patients with juvenile idiopathic arthritis (JIA) and adults with rheumatoid arthritis (RA) were studied.Methods: Anti‐CCP antibodies were determined by enzyme‐linked immunosorbent assay (ELISA) in 59 patients with JIA, 129 adult RA patients, 48 children with diseases other than JIA, 68 adult patients with rheumatic diseases other than RA, and 60 normal adults. Associations between anti‐CCP antibodies and clinical and laboratory parameters were determined by Fisher's exact test.Results: Six of 59 (10.2%) patients with JIA and 71 of 129 (55%) patients with RA were positive for anti‐CCP. Four of five RF‐positive JIA patients and two of 54 RF‐negative JIA patients were positive (p<0.001). One paediatric patient with allergy (0.9%) and two adult patients with rheumatic diseases other than RA (2.3%) were positive. All healthy controls were negative for anti‐CCP. The specificity was 99.1% for JIA and 98.4% for RA. The sensitivity was 10.2% for JIA and 55% for RA. Positive predictive values were 85.7% for JIA and 97.3% for RA and negative predictive values were 66.9% for JIA and 68.5% for RA.Conclusion: The anti‐CCP antibody assay is a valuable tool for the diagnosis of RA and a subset of JIA in Chinese patients. It could be a useful predictive test for joint erosion in JIA of the polyarticular RF‐positive subset and may be influential in the choice of the best therapeutic strategy in patients with recent‐onset arthritis.

Adalimumab is a monoclonal antibody produced by DNA recombination technology, and is the first human monoclonal antibody against human tumor necrosis factor (TNF)-α in the world. Adalimumab binds with high affinity and specificity to soluble TNF-α and normalizes its biological action. The clinical development of adalimumab started in Europe. Adalimumab was approved for the treatment of rheumatoid arthritis (RA) in December 2002 in the United States and in September 2003 in the European Union. Since then, adalimumab has been approved for the expanded indications of psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis (Ps), and juvenile idiopathic arthritis (JIA) in the United States and the European Union, and it is now used widely for the treatment of these diseases. In Japan, adalimumab was approved for the treatment of RA in April 2008, and its use was approved for the indications of Ps and PsA in January 2010, and for CD and AS in October 2010. In Japan, children who have been diagnosed and treated according to the "Proposal for juvenile idiopathic arthritis guidance on diagnosis and treatment for primary care pediatricians and nonpediatric rheumatologists (2007)" (published in this journal in 2007; see reference 1 in the main text), but who have responded poorly to treatment must move onto the next stage of treatment. Such treatments include biological drugs, which, however, should be used with strict adherence to the indications and exclusion criteria and should be used, for the time being, only by physicians trained in how to use them. In Japan, adalimumab was approved for the treatment of JIA in July 2011. Although this drug has brought about a revolutionary advance in the treatment of JIA, it is our task to maximize its therapeutic effects and minimize its toxic effects. The guidance presented here define the indications, exclusion criteria, usage, and evaluation criteria of adalimumab for the treatment of polyarticular JIA.